A Symptom Management Efficacy Study to Reduce Distal Neuropathic Pain

末梢感觉周围神经病(DSP)是一种影响生活质量的慢性、衰弱的疼痛状态 在20%-50%的艾滋病毒携带者中。用于控制DSP疼痛的处方治疗，如非麻醉性药物和 麻醉性止痛药、抗抑郁药和抗惊厥药在很大程度上无效。我们的研究，使用 针灸(Acu/Moxa)治疗HIV-DSP疼痛，显示出作为一种有效治疗方法的前景。 这项研究建立在初步数据的基础上，以测试一种新的方法，Acu/Moxa，以管理慢性下肢DSP 艾滋病毒携带者成人的疼痛。影响：目前还没有FDA批准的药物用于HIV的这一适应症。有效 对于这一人群来说，DSP疼痛的管理是一个尚未满足的治疗需求。这项研究的结果可以提供 有证据的非药物治疗选择的患者和临床医生来处理这种痛苦 条件。文献，我们的临床经验，我们的初步研究和我们团队的实力为我们提供了一个 进行一项严格的、随机、盲目、安慰剂对照的临床试验 符合COSORT和STRICTA指南的ACU/MOXA治疗HIV DSP疼痛。 与HIV相关的下肢DSP疼痛的受试者被随机分为四种情况之一：1)标准(固定) 方案Acu/Moxa，2)个性化(定制)方案Acu/Moxa，3)假Acu/安慰剂Moxa(对照)，或4) 等待列表(控制)。受试者参加为期六周的每周两次治疗和3次非治疗随访 在第9周、第11周和第15周进行治疗。所有受试者都由盲人针灸诊断师(DA)和 那些被分配到条件1、2和3的人由不盲目的针灸治疗师(TA)进行治疗。 具体目标是：#1确定每周平均疼痛(Gracely Pain Scale)在结束时的组差异 治疗(TX)和随访结束(F/U)；SA#2确定两组在特定情况下改善的差异 感觉症状(主观周围神经病变筛查和神经感觉测试(NST))和 患者评定的有效性(临床全球改善、NIH Promis疼痛强度和健康相关 TX和F/U的生活质量(MOS-HIV)；SA#3确定安全概况中的组差异；SA#4， 探讨基线测量、中医诊断、NST和止痛药使用如何预测治疗反应。 受试者内纵向变化的群体差异的初步意向分析 TX和F/U对重复测量使用线性混合模型(LMMRm)，对DA、治疗具有固定效果 组、时间、它们与协变量的交互作用以调整基线(SA#1和 SA#2)。初步研究估计格雷斯利疼痛等级和20%磨损率的“中等”效应大小 表示需要196个受试者达到80%的功率和5%的阿尔法来检测一个活动对象的优势 一种是控制治疗，另一种是积极治疗。横截面关联和纵向关联 在中医诊断、NST评估和止痛药使用之间存在患者评级的变化 有效性将对目标4使用多重相关/回归。

Distal sensory peripheral neuropathy (DSP) is a chronic, debilitating painful condition affecting quality of life in 20%-50% of persons living with HIV. Treatments prescribed to manage DSP pain, such as nonnarcotic and narcotic analgesics, antidepressants and anticonvulsants, are largely ineffective. Our studies, using acupuncture and moxibustion (Acu/Moxa) to manage HIV DSP pain, show promise as an effective therapy. This study builds on preliminary data to test a novel approach, Acu/Moxa, to manage chronic lower-limb DSP pain in adults living with HIV. IMPACT: there are no FDA-approved agents for this indication in HIV. Effective management of DSP pain is an unmet therapeutic need for this population. Results from this study can provide patients and clinicians with an evidenced-based non-pharmacologic therapeutic option to manage this painful condition. The literature, our clinical experience, our preliminary studies and strength of our team provide a strong rationale to conduct a rigorous, randomized, blinded, placebo-controlled clinical trial of the efficacy of Acu/Moxa for HIV DSP pain that adheres to the CONSORT and STRICTA guidelines. Subjects with HIV-related lower limb DSP pain are randomized to one of four Conditions: 1) Standard (fixed) protocol Acu/Moxa, 2) Individualized (tailored) protocol Acu/Moxa, 3) Sham Acu/Placebo Moxa (control), or 4) WaitList (control). Subjects attend six weeks of twice weekly treatment sessions and 3 non-treatment follow-up sessions at weeks 9, 11, and 15. All subjects are assessed by a blinded diagnostic acupuncturist (DA) and those assigned to Conditions 1, 2 and 3 receive treatments by an unblinded treating acupuncturist (TA). Specific Aims are: #1 determine group differences in weekly average pain (Gracely Pain Scale) at the end of treatment (Tx) and end of follow-up (F/U); SA#2 determine group differences in improvement in specific sensory symptoms (Subjective Peripheral Neuropathy Screen and neurological sensory testing (NST)) and patient-rated effectiveness (Clinical Global Improvement, NIH PROMIS Pain Intensity and Health-Related Quality of Life (MOS-HIV)) at Tx and F/U; SA#3 determine group differences in safety profiles; and SA#4, explore how baseline measures, TCM diagnoses, NST and pain medication use predict response to treatment. The primary intent-to-treat analysis of group differences in within-subject longitudinal change from baseline to Tx and F/U uses linear mixed models for repeated measures (LMMrm) with fixed effects for DA, treatment group, time, their interactions with covariate adjustment for the level of the outcome at baseline (SA#1 & SA#2). Preliminary studies estimate of “medium” effect sizes for the Gracely Pain Scale and 20% attrition indicates the need for 196 subjects to achieve 80% power and 5% alpha to detect the superiority of one active treatment to control, and one active treatment to the other. Cross-sectional and longitudinal associations between TCM diagnoses, NST assessments and pain medication use with change in patient-rated effectiveness will use multiple correlation/regression for aim #4.